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Diabetes mellitus is a uniquely interesting disorder to study from an epidemiologic perspective. Information that can be gathered from carefully designed and executed epidemiologic studies carried out on a population-based group of individuals with insulin-dependent diabetes mellitus (IDDM) provides insight into this disorder that cannot be obtained by traditional methods of basic or clinical research. The application of epidemiology as an investigative tool can be illustrated in 3 important areas of diabetes mellitus: (1) the etiology of IDDM, (2) the natural history or clinical course of IDDM, and (3) long-term complications of IDDM.

Previous work has shown that glucose oxidase can be immobilized on platinum to give an electrode that responds potentiometrically to glucose over the clinically useful range of about 10-250 mg glucose/100 mL. The present studies were carried out with electrochemically pretreated platinum and with gold or porous graphite substituted for the platinum support. The presence of the enzyme gave a significantly enhanced potentiometric response over that obtained with the bare support for both the pretreated platinum and the porous graphite, but not with gold. However, with platinum the potentiometric response became more negative with increasing glucose concentration. With porous graphite, the potential changed in the positive direction as the glucose concentration was increased. Hysteresis was demonstrated for the platinum-enzyme electrode. Mass transfer measurements with a rotating ring-disc electrode (RRDE) showed measurable diffusional resistances to the transport of a model electroactive compound (potassium ferrocyanide) through a matrix of immobilized enzyme attached to the disc of the RRDE. These results are part of a larger study to define the source of the potentiometric response by examining the roles of the support and the mass transfer resistances through the immobilized enzyme matrix.

Much debate has taken place over the mode(s) of inheritance of insulin-dependent diabetes mellitus (IDDM) and the possibility of etiological heterogeneity. We have analyzed the disease status (IDDM) and genetic marker (HLA-A/B haplotype) data from 61 multiple-case IDDM families ascertained through two registries in the Pittsburgh, Pennsylvania, area. Linkage analysis results were similar for five previously published simple models of transmission. No heterogeneity could be detected on the basis of the total sample or when the sample was categorized according to the proband's HLA-B or HLA-DR type. In contrast, categorizing the families by generation(s) of the affected individuals revealed differences in the linkage analysis results. Families with affected siblings only (N = 38) showed strong evidence for close linkage for all models. Families with a parent and siblings affected (N = 6) showed evidence against close linkage between HLA-B and IDDM for some models.

This study, which included 154 participants in a 10-yr follow-up study of diabetes complications, was conducted to evaluate AlbuSure (a qualitative test designed to detect urinary albumin concentrations greater than 0.03 g/L) for its ability to discriminate between albumin concentrations above and below the manufacturer's concentration threshold and to identify individuals at increased risk for developing diabetic nephropathy (i.e., those with albumin excretion rate [AER] greater than 0.0288 g/24 h). The reproducibility of AlbuSure results was also evaluated. The results of these evaluations were examined by three different types of urine collections (24 h, overnight, and timed postclinic) and overall. AlbuSure's validity was examined by comparing its results to immunonephelometrically measured concentrations and AER. When compared to albumin concentration, AlbuSure had an overall sensitivity of 81.8%, specificity of 94.8%, and positive predictive value of 90.6%. AlbuSure's sensitivity was lower (71.4%) when compared with AER; however, this was higher than the sensitivity achieved by dipsticks against AER (50.7%). On testing urine samples stored for 3 days at 4 degrees C, AlbuSure results were 100% reproducible after 1 day and had an overall reproducibility of 92% after 3 days. When urine was retested after 3 and 15 mo of storage at -70 degrees C, AlbuSure was greater than or equal to 90% reproducible, with some of the differing results attributable to corresponding changes in albumin concentration. The overnight sample appeared to be the sample of choice for testing with AlbuSure in that it showed excellent reproducibility and the highest sensitivity (compared to both albumin concentration and AER).

Glycosylated haemoglobin (HbA1) was measured serially by microcolumn chromatography in 38 children with newly diagnosed insulin-dependent diabetes. Initial HbA1 levels of 13.6 +/- 0.5% fell signficiantly from day 0 (prior to therapy) both to day 1 (1.6 +/- 0.2% decrease) and to day 3-5 (2.6 +/- 0.4% decrease) (P < 0.001). This drop correlated closely with changes in blood glucose (P < 0.001), less closely and inversely with plasma bicarbonate levels (P < 0.01), but not with prior duration of symptoms or changes in serum cholesterol and triglyceride concentrations. HbA1 levels reached a nadir of 8.2 +/- 0.3% 3 weeks to 6 months after diagnosis, and correlated with decreasing insulin dosage (P < 0.001). HbA1 levels rose again to 11.4 +/- 0.5% in 21 patients followed for more than 3-6 months. Our results indicate that (1) HbA1 level change rapidly during initial stabilization of insulin-dependent diabetes suggesting that glycosylation may not be entirely irreversible, and (2) HbA1 levels are consistent with clinical assessment of control during remission and postremission phases.

A case-control study examining the 1-yr motor vehicle accident experiences of 158 insulin-dependent diabetes mellitus (IDDM) cases and 158 nondiabetic siblings was undertaken to evaluate the risk of motor vehicle accidents among drivers with IDDM. In multivariate analyses the overall accident risk of the cases and control subjects did not differ significantly. Female diabetic drivers, however, showed a marked increased risk for motor vehicle accidents. The accident risk among female cases was five times higher than among the female control subjects (P less than .05). Age and marital status were also significantly associated with accident probability in the multivariate model. The results suggest that IDDM could have an effect on the accident rate of diabetic drivers, particularly women. However, the traditional risk factors for automobile accidents, i.e., age and marital status, appear to have an equally strong influence on accident occurrence. Further studies are needed to 1) document the role of IDDM in accidents among representative samples of the IDDM population and 2) properly evaluate the licensing restrictions recommended for diabetic drivers.

End Stage Renal Disease (ESRD) is a common consequence of diabetic nephropathy (DN). DN is the major cause of death in patients with IDDM, accounting for greater than 40% of deaths with this form of diabetes. There is no clearly documented therapeutic technique that will prevent or reverse progressive renal damage in IDDM. While pancreatic transplantation and "cure" of diabetes in experimental animals may be associated with some histological reversal of renal pathology, this has not been documented in humans. Most studies agree that once diabetic renal disease is present (as documented by proteinuria), progression is inevitable, albeit the rate of progression may be altered by different therapeutic methods. There is considerable hope that "tight metabolic control" will prevent the initial damage that leads to DN and ESRD, but evidence remains inconclusive. There is some evidence that careful monitoring for microalbuminuria will allow for very early detection of damage and alterations in therapy. Our studies have documented a decrease in both morbidity and mortality in IDDM in patients who have been competitive athletes, suggesting that promotion of physical fitness may be a valuable means of delaying progression of renal disease while control of BP delays progression. Early detection and aggressive therapy is recommended. Some studies utilizing diets low in sodium and/or protein appear beneficial but more studies are needed before pediatric application.

Although children with IDDM are at a sevenfold increased risk of dying when compared with nondiabetic individuals of the same age, the factors associated with the excess in mortality remain unclear. To investigate potential determinants of mortality among IDDM patients, a case-control study was conducted. These retrospectively obtained data indicated that shorter relative height at onset, frequent diabetes-related readmissions, the presence of diabetes complications, a family history of diabetes, premature familial mortality, no participation in school team sports, and a lower level of education were related to subsequent mortality among males. Among females, however, a shorter duration of diabetes clinic attendance and the presence of diabetes complications were the only significant associations to mortality.